Yoopan Nattaporn, Watcharasit Piyajit, Wongsawatkul Orapin, Piyachaturawat Pawinee, Satayavivad Jutamaad
Toxicology Graduate Programme, Faculty of Science, Mahidol University, Rama 6 Rd., Bangkok 10400, Thailand.
Toxicol Lett. 2008 Jan 30;176(2):157-61. doi: 10.1016/j.toxlet.2007.11.002. Epub 2007 Nov 21.
Cadmium (Cd) has been reported to induce hypertension in both humans and animals; however, its mechanism has not been clearly elucidated. Vascular tone is one of the factors contributing to hypertension. This study was conducted to investigate the effects of Cd exposure on vascular muscarinic receptor responses to acetylcholine (ACh) in isolated aortas. Male Sprague-Dawley rats were exposed to Cd via drinking water (5, 10 and 50 ppm) for 3 months. Cd 10 and 50 ppm exposure caused significant decreases in the sensitivity of vascular muscarinic receptors to ACh. However, Cd exposure did not alter the vascular relaxation induced by sodium nitroprusside (SNP) which is a nitric oxide donor. Consistent with the reduction of ACh-induced relaxation, treatment with Cd decreased endothelial nitric oxide synthase (eNOS) protein level in blood vessels. These results suggested that Cd suppressed ACh-induced vascular relaxation by interfering with muscarinic receptor function, and its downstream signaling pathway may be one of the contributing factors for the development of hypertension.
据报道，镉（Cd）可在人和动物中诱发高血压，但其机制尚未完全阐明。血管张力是导致高血压的因素之一。本研究旨在探讨镉暴露对离体主动脉中血管毒蕈碱受体对乙酰胆碱（ACh）反应的影响。将雄性Sprague-Dawley大鼠通过饮用水（5、10和50 ppm）暴露于镉中3个月。暴露于10和50 ppm镉会导致血管毒蕈碱受体对ACh的敏感性显著降低。然而，镉暴露并未改变由一氧化氮供体硝普钠（SNP）诱导的血管舒张。与ACh诱导的舒张作用降低一致，镉处理降低了血管中内皮型一氧化氮合酶（eNOS）蛋白水平。这些结果表明，镉通过干扰毒蕈碱受体功能抑制ACh诱导的血管舒张，其下游信号通路可能是导致高血压发生的因素之一。
